Phenol → 1-(4-Pyridinylamino)-2-pyrrolidinone
Reaction equation
[NH2:1][N:2]1[CH2:6][CH2:5][CH2:4][C:3]1=[O:7].C1(O)C=CC=CC=1.Cl.Br[C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1>>[N:20]1[CH:21]=[CH:22][C:17]([NH:1][N:2]2[CH2:6][CH2:5][CH2:4][C:3]2=[O:7])=[CH:18][CH:19]=1Participants
Conditions
- Temperature
- 140 °C
Procedure
A slurry consisting of 1-amino-2-pyrrolidinone (7.40 g), phenol (17.8 g), and 4-bromopyridine hydrochloride (15.8 g) was heated in a 140° C. oil bath for 70 minutes under nitrogen. The resulting solution was cooled to room temperature and purified via flash column chromatography (silica gel, 2% Et3N/0-50% MeOH/EtOAc) and preparative high performance liquid chromatography (HPLC) (silica gel, 10% MeOH/DCM). The resulting product fractions were concentrated and the product was redissolved in dichloromethane and sat. aqueous sodium bicarbonate. Exhaustive extraction of the aqueous layer afforded the pure product (free of triethyl amine salts). Recrystallization from dichloromethane/ether afforded 2.10 g (16%) of 1-(4-pyridinylamino)-2-pyrrolidinone, m.p. 177°-179.5° C.
Workup
- temperatureThe resulting solution was cooled to room temperature
- custompurified via flash column chromatography (silica gel, 2% Et3N/0-50% MeOH/EtOAc) and preparative high performance liquid chromatography (HPLC) (silica gel, 10% MeOH/DCM)
- concentrationThe resulting product fractions were concentrated
- dissolutionthe product was redissolved in dichloromethane
- extractionExhaustive extraction of the aqueous layer
- customafforded the pure product (free of triethyl amine salts)
- customRecrystallization from dichloromethane/ether
Sources & evidence
- ORD record
- ord-9db8f35db0754207acb027988432eb80
- Source dataset
- uspto-grants-1991_02
- Patent number
- US04994472
Reaction notes
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